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1.  Does regional compared to local anaesthesia influence outcome after arteriovenous fistula creation? 
Trials  2013;14:263.
An arteriovenous fistula is the optimal form of vascular access in patients with end-stage renal failure requiring haemodialysis. Unfortunately, approximately one-third of fistulae fail at an early stage. Different anaesthetic techniques can influence factors associated with fistula success, such as intraoperative blood flow and venous diameter. A regional anaesthetic brachial plexus block results in vasodilatation and improved short- and long-term fistula flow compared to the infiltration of local anaesthetic alone. This, however, has not yet been shown in a large trial to influence long-term fistula patency, the ultimate clinical measure of success.
The aim of this study is to compare whether a regional anaesthetic block, compared to local anaesthetic infiltration, can improve long-term fistula patency.
This study is an observer-blinded, randomised controlled trial. Patients scheduled to undergo creation of either brachial or radial arteriovenous fistulae will receive a study information sheet, and consent will be obtained in keeping with the Declaration of Helsinki. Patients will be randomised to receive either: (i) an ultrasound guided brachial plexus block using lignocaine with adrenaline and levobupivicaine, or (ii) local anaesthetic infiltration with lignocaine and levobupivicaine.
A total of 126 patients will be recruited. The primary outcome is fistula primary patency at three months. Secondary outcomes include primary patency at 1 and 12 months, secondary patency and fistula flow at 1, 3 and 12 months, flow on first haemodialysis, procedural pain, patient satisfaction, change in cephalic vein diameter pre- and post-anaesthetic, change in radial or brachial artery flow pre- and post-anaesthetic, alteration of the surgical plan after anaesthesia as guided by vascular mapping with ultrasound, and fistula infection requiring antibiotics.
No large randomised controlled trial has examined the influence of brachial plexus block compared with local anaesthetic infiltration on the long-term patency of arteriovenous fistulae. If the performance of brachial plexus block increases fistulae patency, this will have significant clinical and financial benefits as the number of patients able to commence haemodialysis when planned should increase, and the number of “redo” or revision procedures should be reduced.
Trial registration
This study has been approved by the West of Scotland Research Ethics Committee 5 (reference no. 12/WS/0199) and is registered with the database (reference no. NCT01706354).
PMCID: PMC3765116  PMID: 23958289
Fistula; Patency; Flow; Anaesthetic; Local; Nerve block; Renal failure
2.  Cognitive and functional competence after anaesthesia in patients aged over 60: controlled trial of general and regional anaesthesia for elective hip or knee replacement. 
BMJ : British Medical Journal  1990;300(6741):1683-1687.
OBJECTIVE--To determine the influence of general or regional anaesthesia on long term mental function in elderly patients. DESIGN--Prospective study of patients randomly allocated to receive general or regional anaesthesia. SETTING--The patients' homes and a large teaching hospital in Cardiff. SUBJECTS--146 Patients aged 60 and over scheduled for elective hip or knee replacement. MAIN OUTCOME MEASURES--Scores achieved in tests of cognitive function and functional competence. RESULTS--72 Patients were allocated to receive general anaesthesia and 74 regional anaesthesia. Anaesthetic technique did not influence the duration of the operation, time to mobilisation postoperatively, requirements for analgesia after the operation, or duration of stay in hospital. Three months after the operation there was an improvement in the score for the recognition component (76 ms, 95% confidence interval 9 to 144) and the response component (82 ms, 5 to 158) of the choice reaction time in the group receiving general anaesthesia compared with the group receiving regional anaesthesia. This was the only significant difference between the two groups in the assessments of cognitive and functional competence. Eleven patients receiving regional anaesthesia and 12 receiving general anaesthesia reported that their memory and concentration were worse than before the operation, but this was not confirmed by testing. CONCLUSION--Cognitive and functional competence in elderly patients was not detectably impaired after either general or regional anaesthesia when attention was paid to the known perioperative influences on mental function.
PMCID: PMC1663336  PMID: 2390547
3.  Anaesthetics-Induced Neurotoxicity in Developing Brain: An Update on Preclinical Evidence 
Brain Sciences  2014;4(1):136-149.
Every year millions of young people are treated with anaesthetic agents for surgery and sedation in a seemingly safe manner. However, growing and convincing preclinical evidence in rodents and nonhuman primates, together with recent epidemiological observations, suggest that exposure to anaesthetics in common clinical use can be neurotoxic to the developing brain and lead to long-term neurological sequelae. These findings have seriously questioned the safe use of general anaesthetics in obstetric and paediatric patients. The mechanisms and human applicability of anaesthetic neurotoxicity and neuroprotection have remained under intense investigation over the past decade. Ongoing pre-clinical investigation may have significant impact on clinical practice in the near future. This review represents recent developments in this rapidly emerging field. The aim is to summarise recently available laboratory data, especially those being published after 2010, in the field of anaesthetics-induced neurotoxicity and its impact on cognitive function. In addition, we will discuss recent findings in mechanisms of early-life anaesthetics-induced neurotoxicity, the role of human stem cell-derived models in detecting such toxicity, and new potential alleviating strategies.
PMCID: PMC4066242  PMID: 24961704
anaesthetics; neuroapoptosis; neurotoxicity; neonates; developing brain
4.  Feasibility and Pilot Study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) Project 
Animal studies have documented that exposure of the developing brain to commonly used anesthetic agents induce neurotoxicity and late abnormal neurobehavioral functions as adults. Results from clinical studies have all been performed using existing datasets, and produced inconsistent results. To provide more definitive evidence to address the clinical relevance of anesthetic neurotoxicity in children, an interdisciplinary team of investigators designed and developed the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project. We present pilot study results in 28 sibling pairs recruited and tested at Columbia University Medical Center (CUMC) and Children’s Hospital of Boston (CHB) for the PANDA project.
The PANDA project uses an ambi-directional cohort design. We performed prospective neuropsychological assessment in 28 exposed-unexposed sibling pairs ages 6–11 years old. The exposed siblings were ASA 1 or 2 and had received a single episode of anesthesia for inguinal hernia repair prior to age 36 months and the unexposed siblings had no anesthesia before age 36 months. All sibling pairs were English speaking and were 36 weeks gestational age or greater. Each sibling pair underwent direct testing using WASI and NEPSY II, and the parents completed questionnaires related to behavior using CBCL and Conners’ rating. Data are presented as means ± SD. We conducted descriptive analyses of demographic data. We compared exposed and unexposed sibling groups on WASI and NEPSY II, and total and T-scores from CBCL and Conners’ as continuous data by paired t test between. A P< 0.05 was considered significant.
Following IRB approval for the study at both CUMC and CHB, the full PANDA study protocol was implemented to perform a pilot feasibility study. Our success rate was 96.7% in obtaining detailed medical and anesthesia records in our historical cohort. Scores for verbal IQ (Exposed=106.1±16.3,Unexposed=109.2±17.9), performance IQ (Exposed=109.1±16.0, Unexposed=113.9±15.9) and full IQ (Exposed=108.2±14.0, Unexposed=112.8±16.8) were comparable between siblings. There were no differences between the two groups in T scores for any of the NEPSY II sub-domains, CBCL or Conners’. An abstraction protocol with web-based electronic data capture forms also was developed in conjunction with the International Center for Health Outcomes and Innovation Research (InCHOIR).
The pilot study provided useful information for feasibility to recruit the sample size and to obtain relevant clinical data. For the final study protocol, both the neuropsychological battery and the age range for testing were revised. Our results confirmed the feasibility of our study approach, and yielded pilot data from neuropsychological testing.
PMCID: PMC3475987  PMID: 23076226
Children; Anesthetic neurotoxicity; Neurodevelopment; Outcome
5.  Percutaneous regional compared with local anaesthesia for facial lacerations: a randomised controlled trial 
Objective: Facial lacerations are usually repaired after local infiltration of an anaesthetic agent. Regional nerve blocks of the face offer several theoretical advantages over local infiltration. This study compared the pain of injection and anaesthetic efficacy of percutaneous regional and local anaesthesia for facial lacerations.
Study design: Randomised clinical trial.
Participants: Convenience sample of emergency department patients with facial lacerations requiring suturing in anatomical areas innervated by a regional nerve (supraorbital, infraorbital, or mental).
Interventions: Facial lacerations treated using standard wound care. Lacerations were randomised to local or regional infiltration of lidocaine (lignocaine) 1% with adrenaline (epinephrine) 1:100 000 using a number 27 needle.
Outcomes: Pain of injection on 100 mm visual analogue scale (VAS) and need for rescue anaesthetic infiltration before suturing.
Data analysis: Group comparisons were with Student's t test and χ2 test. This study had 80% power to detect a 20 mm difference in pain of injection (two tailed, α = 0.05).
Results: 36 patients were randomised to local (18) and regional (18) anaesthesia. Mean (SD) age was 20 (14); 19% were female. Groups were similar in baseline characteristics. Patients in the regional anaesthesia group experienced more pain during infiltration than patients in the local anaesthesia group (42.4 mm v 24.8 mm, mean difference 17.6 mm (95% CI 0.3 to 35.6 mm) and were more likely to require additional infiltration of a local anaesthetic (28% v 0%, (95% CI 6% to 50%)) than patients in the local anaesthetic group.
Conclusions: Local infiltration of anaesthetics for facial lacerations is less painful and results in more effective anaesthesia than percutaneous regional infiltration.
PMCID: PMC1726525  PMID: 15611540
6.  The effects of anaesthesia on the developing brain: a summary of the clinical evidence 
F1000Research  2013;2:166.
Introduction: There is data amassing in the literature regarding the potentially adverse effects of anaesthesia exposure on the developing human brain. The purpose of this article is to summarise current relevant data from clinical studies in this area.
Methods: Articles from journals written in English were searched for using PubMed, Ovid and Medline. Keywords used included: brain (newborn, infant, child and neonate), neurodegeneration, apoptosis, toxicity, neurocognitive impairment (developmental impairment and learning disorders) and anaesthesia (intravenous, inhalational and sedation).
Results: From the initial search, 23 articles were identified as potentially relevant, with publication dates spanning from 1978 to 2012.  Twelve studies were deemed irrelevant to the research questions. The results of neurocognitive assessment from eight of the remaining eleven studies had showed some differences in the performances of children exposed to anaesthesia. The control population in these studies was highly variable. The age at which the subjects were exposed to anaesthesia ranged from prenatal to 4 years in the majority of studies with one including children aged up to 12 years when exposed.
Discussion: Although there is clinical data suggesting a possible detrimental effect, the evidence is best considered preliminary and inconclusive at this stage. Many of the outcome measures were lacking in specificity and standardization in most cases. Parents should be counselled to not avoid necessary invasive procedures for fear of a currently ill-defined risk.  However, deferral of elective procedures beyond the first few years of life should be contemplated.
PMCID: PMC3829131  PMID: 24327918
7.  The effects of anaesthesia on the developing brain: a summary of the clinical evidence 
F1000Research  2013;2:166.
Introduction: There is data amassing in the literature regarding the potentially adverse effects of anaesthesia exposure on the developing human brain. The purpose of this article is to summarise current relevant data from clinical studies in this area.
Methods: Articles from journals written in English were searched for using PubMed, Ovid and Medline. Keywords used included: brain (newborn, infant, child and neonate), neurodegeneration, apoptosis, toxicity, neurocognitive impairment (developmental impairment and learning disorders) and anaesthesia (intravenous, inhalational and sedation).
Results: From the initial search, 23 articles were identified as potentially relevant, with publication dates spanning from 1978 to 2012.  Twelve studies were deemed irrelevant to the research questions. The results of neurocognitive assessment from eight of the remaining eleven studies had showed some differences in the performances of children exposed to anaesthesia. The control population in these studies was highly variable. The age at which the subjects were exposed to anaesthesia ranged from prenatal to 4 years in the majority of studies with one including children aged up to 12 years when exposed.
Discussion: Although there is clinical data suggesting a possible detrimental effect, the evidence is best considered preliminary and inconclusive at this stage. Many of the outcome measures were lacking in specificity and standardization in most cases. Parents should be counselled to not avoid necessary invasive procedures for fear of a currently ill-defined risk.  However, deferral of elective procedures beyond the first few years of life should be contemplated.
PMCID: PMC3829131  PMID: 24327918
8.  Obstructive sleep apnoea syndrome in children and anaesthesia 
Indian Journal of Anaesthesia  2010;54(1):18-23.
Obstructive sleep apnoea syndrome (OSAS) is a common medical disorder among adults, which is increasingly being recognized in children too. It is a breathing disorder characterized by upper airway obstruction with or without intermittent complete obstruction that disrupts normal breathing during sleep. Anatomical and neuromuscular disorders are mainly responsible for this disorder. This disorder leads to a state of chronic hypoxemia, which has significant cardiac, pulmonary and central nervous system implications. Diagnosis of OSAS is based on thorough history and clinical examination along with appropriate sleep studies including polysomnography. The mainstay of treatment of paediatric OSAS is adenotonsillectomy. Good anaesthetic practice in Paediatric patients with OSAS revolves around good and ideal airway management. Early detection of airway obstruction, intense monitoring to warn of impending airway problems and appropriate and early intervention of airway compromise are good anaesthetic practices. Coexisting medical problems should be adequately addressed and safe analgesic techniques in the perioperative period go towards improving outcomes in patients with paediatric OSAS.
PMCID: PMC2876895  PMID: 20532066
Anaesthesia; children; OSAS
9.  The effect of temperature on the discomfort caused by topical local anaesthesia. 
The warming of local anaesthetic solutions to reduce the pain felt on injection is common practice in a number of medical sub-specialties. A study was undertaken to assess the effect of temperature on the discomfort caused by local anaesthetic eye drops. Tropical anaesthetics amethocaine 1%, oxybuprocaine 0.4% and lignocaine 4% were studied, and after the application of strict exclusion criteria 60 patients were selected, 20 patients for each anaesthetic. Each patient group received a topical anaesthetic at 42 degrees C in one eye and at room temperature in the other. A 10 point visual analogue scale was used to assess the discomfort experienced. No statistically significant difference was found between the discomfort caused by drops at each temperature for any of the three anaesthetics studied. There appears no benefit in warming topical anaesthetic agents prior to their use.
PMCID: PMC1295423  PMID: 8786596
10.  Remifentanil infusion as a modality for opioid-based anaesthesia in paediatric practice 
Indian Journal of Anaesthesia  2010;54(4):318-323.
This study was designed to compare the intra-operative and post-operative analgesic requirements and side effects of using fentanyl infusion versus remifentanil infusion during short-duration surgical procedures in children. The study comprised of 40 children randomly allocated into two equal groups: fentanyl (F-group) or remifentanil (R-group). Both were administered a continuous intravenous (i.v.) infusion. Anaesthetic recovery was assessed using the Brussels sedation scale every 5 min from the time of entry till discharge from recovery room. Post-operative analgesia was assessed throughout the first three post-operative (PO) hours using observational pain–discomfort scale (OPS) and adverse events were recorded. Haemodynamic variables showed a non-significant difference between both the groups. Patients who received remifentanil showed significantly shorter time to spontaneous respiration, eye opening, extubation and verbalization compared to those who received fentanyl. Discharge time was significantly shorter in R-group, and 18 patients fulfilled criteria for recovery-room discharge at ≤25 min with a significant difference in favour of remifentanil. Fentanyl provided significantly better PO analgesia than remifentanil and children in F-group showed a significantly lower mean cumulative OPS record than those in R-group; however, the number of patients requiring rescue analgesia did not show a significant difference between both the groups. Two cases in F-group and one in R-group had bradycardia, one case in R-group had mild hypotension and PO vomiting had occurred in three patients in the F-group and two patients in the R-group. In conclusion, remifentanil is appropriate for opioid-based anaesthesia for paediatric patients as it provides haemodynamic stability and rapid recovery with minimal post-operative side effects.
PMCID: PMC2943701  PMID: 20882174
Opioid based; paediatric; remifentanil
11.  Pain and Efficacy Rating of a Microprocessor-Controlled Metered Injection System for Local Anaesthesia in Minor Hand Surgery 
Pain Research and Treatment  2011;2011:362396.
Purpose. Little attention has been given to syringe design and local anaesthetic administration methods. A microprocessor-controlled anaesthetic delivery device has become available that may minimize discomfort during injection. The purpose of this study was to document the pain experience associated with the use of this system and to compare it with use of a conventional syringe. Methods. A prospective, randomized clinical trial was designed. 40 patients undergoing carpal tunnel release were block randomized according to sex into a two groups: a traditional syringe group and a microprocessor-controlled device group. The primary outcome measure was surgical pain and local anaesthetic administration pain. Secondary outcomes included volume of anaesthetic used and injection time. Results. Analysis showed that equivalent anaesthesia was achieved in the microprocessor-controlled group despite using a significantly lower volume of local anaesthetic (P = .0002). This same group, however, has significantly longer injection times (P < .0001). Pain during the injection process or during surgery was not different between the two groups. Conclusions. This RCT comparing traditional and microprocessor controlled methods of administering local anaesthetic showed similar levels of discomfort in both groups. While the microprocessor-controlled group used less volume, the total time for the administration was significantly greater.
PMCID: PMC3197004  PMID: 22110923
12.  Differential Effects of Anaesthesia on the phMRI Response to Acute Ketamine Challenge 
Pharmacological-challenge magnetic resonance imaging (phMRI) is powerful new tool enabling researchers to map the central effects of neuroactive drugs in vivo. To employ this technique pre-clinically, head movements and the stress of restraint are usually reduced by maintaining animals under general anaesthesia. However, interactions between the drug of interest and the anaesthetic employed may potentially confound data interpretation. NMDA receptor (NMDAR) antagonists used widely to mimic schizophrenia have recently been shown to interact with the anaesthetic halothane. It may be the case that neural and cerebrovascular responses to NMDAR antagonists are dependent on the types of anaesthetic used.
We compared the phMRI response to NMDAR antagonist ketamine in rats maintained under α-chloralose to those under isoflurane anaesthesia. A randomized placebo/vehicle controlled design was used in each of the anaesthetic groups.
Changes in the anaesthetic agent resulted in two very different profiles of activity. In the case of α-chloralose, positive activations in cortical and sub-cortical structures reflected a response which was similar to patterns seen in healthy human volunteers and metabolic maps of conscious rats. However, the use of isoflurane completely reversed such effects, causing widespread deactivations in the cortex and hippocampus.
This study provides initial evidence for a drug-anesthetic interaction between ketamine and isoflurane that is very different from responses to α-chloralose-ketamine.
PMCID: PMC3378209  PMID: 22737655
Anaesthesia; anesthesia; NMDA; ketamine; schizophrenia; α-chloralose; isoflurane; phMRI; fMRI; BOLD; rat
13.  Topical anaesthesia for children's lacerations: an acceptable approach? 
OBJECTIVE--To compare the anaesthetic properties of conventional intradermal 1% plain lignocaine with a topical gel preparation of adrenaline (1:2000) and cocaine (4.7%) for use in treatment of children's lacerations. METHODS--Children aged 3-16 years with lacerations (not of the digits or mucous membranes) were consecutively assigned to receive either adrenaline and cocaine (AC) or lignocaine. Pain scores, as perceived by patients, parents, and staff, were measured conventionally using Wong Baker faces and visual analogue scales on administration of the local anaesthetic and on suturing the wound in the AC group (n = 56) and the lignocaine group (n = 51). RESULTS--Mean and median pain scores on administration of the anaesthetic in the AC group were significantly lower than in the lignocaine group as perceived by patient (P < 0.001), parent (P < 0.001), and staff (P < 0.001). There was no significant difference in mean and median pain scores between the two groups on suturing the wounds, as perceived by patient, parent and staff. There was a significantly higher number of "failed" anaesthetics (pain scores 8-10) in the lignocaine group (P < 0.01). On direct questioning the overall procedure was considered acceptable by 84.5% of parents in the AC group compared with 61% of parents in the lignocaine group (P < 0.01). There were no significant complications in either group. CONCLUSIONS--Topical AC should be considered the local anaesthetic of first choice for suturing appropriate children's lacerations.
PMCID: PMC1342653  PMID: 8653235
14.  Multimodal system designed to reduce errors in recording and administration of drugs in anaesthesia: prospective randomised clinical evaluation 
Objective To clinically evaluate a new patented multimodal system (SAFERSleep) designed to reduce errors in the recording and administration of drugs in anaesthesia.
Design Prospective randomised open label clinical trial.
Setting Five designated operating theatres in a major tertiary referral hospital.
Participants Eighty nine consenting anaesthetists managing 1075 cases in which there were 10 764 drug administrations.
Intervention Use of the new system (which includes customised drug trays and purpose designed drug trolley drawers to promote a well organised anaesthetic workspace and aseptic technique; pre-filled syringes for commonly used anaesthetic drugs; large legible colour coded drug labels; a barcode reader linked to a computer, speakers, and touch screen to provide automatic auditory and visual verification of selected drugs immediately before each administration; automatic compilation of an anaesthetic record; an on-screen and audible warning if an antibiotic has not been administered within 15 minutes of the start of anaesthesia; and certain procedural rules—notably, scanning the label before each drug administration) versus conventional practice in drug administration with a manually compiled anaesthetic record.
Main outcome measures Primary: composite of errors in the recording and administration of intravenous drugs detected by direct observation and by detailed reconciliation of the contents of used drug vials against recorded administrations; and lapses in responding to an intermittent visual stimulus (vigilance latency task). Secondary: outcomes in patients; analyses of anaesthetists’ tasks and assessments of workload; evaluation of the legibility of anaesthetic records; evaluation of compliance with the procedural rules of the new system; and questionnaire based ratings of the respective systems by participants.
Results The overall mean rate of drug errors per 100 administrations was 9.1 (95% confidence interval 6.9 to 11.4) with the new system (one in 11 administrations) and 11.6 (9.3 to 13.9) with conventional methods (one in nine administrations) (P=0.045 for difference). Most were recording errors, and, though fewer drug administration errors occurred with the new system, the comparison with conventional methods did not reach significance. Rates of errors in drug administration were lower when anaesthetists consistently applied two key principles of the new system (scanning the drug barcode before administering each drug and keeping the voice prompt active) than when they did not: mean 6.0 (3.1 to 8.8) errors per 100 administrations v 9.7 (8.4 to 11.1) respectively (P=0.004). Lapses in the vigilance latency task occurred in 12% (58/471) of cases with the new system and 9% (40/473) with conventional methods (P=0.052). The records generated by the new system were more legible, and anaesthetists preferred the new system, particularly in relation to long, complex, and emergency cases. There were no differences between new and conventional systems in respect of outcomes in patients or anaesthetists’ workload.
Conclusions The new system was associated with a reduction in errors in the recording and administration of drugs in anaesthesia, attributable mainly to a reduction in recording errors. Automatic compilation of the anaesthetic record increased legibility but also increased lapses in a vigilance latency task and decreased time spent watching monitors.
Trial registration Australian New Zealand Clinical Trials Registry No 12608000068369.
PMCID: PMC3178276  PMID: 21940742
15.  Pain perception with pH buffered peribulbar anaesthesia: a pilot study 
The British Journal of Ophthalmology  2000;84(9):1041-1044.
AIMS—To determine the relation between pH of anaesthetic solutions and patient perception of pain with peribulbar injection of local anaesthesia.
METHODS—This prospective randomised controlled double blind pilot study involved 60 consecutive patients who received a peribulbar block with either a standard acidic local anaesthetic of 5 ml 2% lignocaine and 5 ml of 0.5% bupivacaine (solution A), or an alkalinised solution composed of the same anaesthetic agents but with a pH of 7.44 (solution B). Before surgery patients were asked to grade the pain of both the preoperative dilating drops and the peribulbar injection using a visual analogue scale.
RESULTS—The mean pain scores were similar in the two treatment groups—slightly higher (4.97) in group B who received the buffered solution, compared with group A (4.84) who received the plain solution. The small difference (−0.13, 95% confidence limits −1.6 and +1.3) was not significant. There was, however, a highly significant association between pain threshold ("drop pain") and injection pain levels (p<0.0001).
CONCLUSION—This study showed no difference in the reduction in the pain experienced by patients undergoing peribulbar anaesthesia with pH buffered local anaesthetic. The study suggests the importance of "pain threshold" as a confounder and also showed the considerable pain felt by some patients on instillation of the preoperative dilating drops.

PMCID: PMC1723663  PMID: 10966962
16.  Peak and averaged bicoherence for different EEG patterns during general anaesthesia 
Changes in nonlinear neuronal mechanisms of EEG generation in the course of general anaesthesia have been extensively investigated in research literature. A number of EEG signal properties capable of tracking these changes have been reported and employed in anaesthetic depth monitors. The degree of phase coupling between different spectral components is a marker of nonlinear EEG generators and is claimed to be an important aspect of BIS. While bicoherence is the most direct measure of phase coupling, according to published research it is not directly used in the calculation of BIS, and only limited studies of its association with anaesthetic depth and level of consciousness have been published. This paper investigates bicoherence parameters across equal band and unequal band bifrequency regions, during different states of anaesthetic depth relating to routine clinical anaesthesia, as determined by visual inspection of EEG.
41 subjects scheduled for day surgery under general anaesthesia were recruited into this study. EEG bicoherence was analysed using average and smoothed-peak estimates calculated over different regions on the bifrequency plane. Statistical analysis of associations between anaesthetic depth/state of consciousness and bicoherence estimates included linear regression using generalised linear mixed effects models (GLMs), ROC curves and prediction probability (Pk).
Bicoherence estimates for the δ_θ region on the bifrequency plane were more sensitive to anaesthetic depth changes compared to other bifrequency regions. Smoothed-peak bicoherence displayed stronger associations than average bicoherence. Excluding burst suppression and large transients, the δ_θ peak bicoherence was significantly associated with level of anaesthetic depth (z = 25.74, p < 0.001 and R2 = 0.191). Estimates of Pk for this parameter were 0.889(0.867-0.911) and 0.709(0.689-0.729) respectively for conscious states and anaesthetic depth levels (comparable BIS estimates were 0.928(0.905-0.950) and 0.801(0.786-0.816)). Estimates of linear regression and areas under ROC curves supported Pk findings. Bicoherence for eye movement artifacts were the most distinctive with respect to other EEG patterns (average |z| value 13.233).
This study quantified associations between deepening anaesthesia and increase in bicoherence for different frequency components and bicoherence estimates. Increase in bicoherence was also established for eye movement artifacts. While identified associations extend earlier findings of bicoherence changes with increases in anaesthetic drug concentration, results indicate that the unequal band bifrequency region, δ_θ, provides better predictive capabilities than equal band bifrequency regions.
PMCID: PMC2998515  PMID: 21092128
17.  Topical anaesthesia for venepuncture. 
Archives of Disease in Childhood  1986;61(11):1132-1134.
A topical anaesthetic cream was tested in a randomised, double blind, placebo controlled trial of 15 children. The severity of pain experienced during venepuncture was assessed, using visual analogue and verbal rating scales. The topical anaesthetic cream was found to be significantly superior to placebo using each form of assessment.
PMCID: PMC1778090  PMID: 3539033
18.  Distinct long-term neurocognitive outcomes after equipotent sevoflurane or isoflurane anaesthesia in immature rats 
BJA: British Journal of Anaesthesia  2013;110(Suppl 1):i39-i46.
Many anaesthetics when given to young animals cause cell death and learning deficits that persist until much later in life. Recent attempts to compare the relative safety or toxicity between different agents have not adequately controlled for the relative dose of anaesthetic given, thereby making direct comparisons difficult.
Isoflurane or sevoflurane were given at 1 minimum alveolar concentration (MAC) for 4 h to postnatal day 7 (P7) rat pups. Beginning at P75 these animals underwent fear conditioning and at P83 Morris water maze testing to assess working memory, short-term memory and early long-term memory using delays of 1 min, 1 h, and 4 h.
No difference between groups was seen in fear conditioning experiments. Morris water maze learning was equivalent between groups, and no difference was seen in working memory. Sevoflurane-treated animals had a deficit in early long-term memory, and isoflurane-treated animals had a deficit in both short-term and early long-term memory.
Both isoflurane and sevoflurane delivered at 1 MAC for 4 h to immature rats caused a deficit in long-term memory. Isoflurane also caused a deficit in short-term memory. Isoflurane might be more detrimental than sevoflurane in very young animals.
PMCID: PMC3695640  PMID: 23592692
animals; isoflurane toxicity; memory drug effects; newborn; sevoflurane toxicity
19.  Psychiatric patient and anaesthesia 
Indian Journal of Anaesthesia  2012;56(1):8-13.
Many patients with psychiatric illnesses are prescribed long-term drug treatment, and the anaesthesiologist must be aware of potential interactions with anaesthetic agents. Psychotropic drugs often given in combination with each other or with other non-psychiatric drugs generally exert profound effects on the central and peripheral neurotransmitter and ionic mechanisms. Hence, prior intake of these drugs is an important consideration in the management of the patient about to undergo anaesthesia and surgery. This article highlights the effects of anaesthetics on patients taking antipsychotics, tricyclic antidepressants, monoamine oxidase inhibitors and lithium carbonate. The risk that should be considered in the perioperative period are the extent of surgery, the patient's physical state, anaesthesia, the direct and indirect effects of psychotropics, risk of withdrawal symptoms and risk of psychiatric recurrence and relapse.
PMCID: PMC3327081  PMID: 22529413
Anaesthetic management; antidepressants; bipolar disorders; depression; schizophrenia
20.  Metabolic effects of CO2 anaesthesia in Drosophila melanogaster 
Biology Letters  2012;8(6):1050-1054.
Immobilization of insects is necessary for various experimental purposes, and CO2 exposure remains the most popular anaesthetic method in entomological research. A number of negative side effects of CO2 anaesthesia have been reported, but CO2 probably brings about metabolic modifications that are poorly known. In this work, we used GC/MS-based metabolic fingerprinting to assess the effect of CO2 anaesthesia in Drosophila melanogaster adults. We analysed metabolic variation of flies submitted to acute CO2 exposure and assessed the temporal metabolic changes during short- and long-term recovery. We found that D. melanogaster metabotypes were significantly affected by the anaesthetic treatment. Metabolic changes caused by acute CO2 exposure were still manifested after 14 h of recovery. However, we found no evidence of metabolic alterations when a long recovery period was allowed (more than 24 h). This study points to some metabolic pathways altered during CO2 anaesthesia (e.g. energetic metabolism). Evidence of short-term metabolic changes indicates that CO2 anaesthesia should be used with utmost caution in physiological studies when a short recovery is allowed. In spite of this, CO2 treatment seems to be an acceptable anaesthetic method provided that a long recovery period is allowed (more than 24 h).
PMCID: PMC3497127  PMID: 22915627
Drosophila; anaesthesia; GC–MS; metabolic fingerprinting; recovery
21.  The Effect of Four Anaesthetic Protocols for Maintenance of Anaesthesia on Trans-Diaphragmatic Pressure in Dogs 
PLoS ONE  2013;8(10):e75341.
The diaphragm is the main inspiratory muscle and the main indicator of diaphragmatic contractility is the trans-diaphragmatic pressure (Pdi). The aim of this clinical study was to determine the effect of four different anaesthetic protocols on Pdi in anaesthetized healthy dogs. Eighty client-owned dogs were recruited in this clinical study. All the animals received dexmedetomidine and morphine as premedication and propofol for induction. Anaesthesia was maintained with one of four protocols: isoflurane (I), isoflurane with CRI of propofol (IP), isoflurane with CRI of fentanyl (IF), and isoflurane with CRI of ketamine (IK). When the surgical plane of anaesthesia was achieved, two balloon catheters were inserted, one into the stomach and one into the mid-third of the oesophagus for Pdi measurement. Pdi value was the highest in groups I (14.9±4.7 mmHg) and IK (15.2±3.5 mmHg) and the lowest in groups IP (12.2±3.2 mmHg) and IF (12.0±5.9 mmHg). There was a statistically significant difference (p = 0.029) between groups IK and IF. PE’CO2 was statistically significantly higher (p<0.0005) in group IF (7.7±0.8 kPa) than in group IK (6.5±0.7 kPa). Isoflurane alone or isoflurane with ketamine for the maintenance of anaesthesia seem to better preserve the respiratory function and the diaphragmatic contractility than isoflurane with either propofol or fentanyl in dogs. Therefore, the use of isoflurane or isoflurane with ketamine may be of benefit when animals with respiratory problems have to be anaesthetized.
PMCID: PMC3790779  PMID: 24124482
22.  Neurobehaviour between birth and 40 weeks’ gestation in infants born <30 weeks’ gestation and parental psychological wellbeing: predictors of brain development and child outcomes 
BMC Pediatrics  2014;14:111.
Infants born <30 weeks’ gestation are at increased risk of long term neurodevelopmental problems compared with term born peers. The predictive value of neurobehavioural examinations at term equivalent age in very preterm infants has been reported for subsequent impairment. Yet there is little knowledge surrounding earlier neurobehavioural development in preterm infants prior to term equivalent age, and how it relates to perinatal factors, cerebral structure, and later developmental outcomes. In addition, maternal psychological wellbeing has been associated with child development. Given the high rate of psychological distress reported by parents of preterm children, it is vital we understand maternal and paternal wellbeing in the early weeks and months after preterm birth and how this influences the parent–child relationship and children’s outcomes. Therefore this study aims to examine how 1) early neurobehaviour and 2) parental mental health relate to developmental outcomes for infants born preterm compared with infants born at term.
This prospective cohort study will describe the neurobehaviour of 150 infants born at <30 weeks’ gestational age from birth to term equivalent age, and explore how early neurobehavioural deficits relate to brain growth or injury determined by magnetic resonance imaging, perinatal factors, parental mental health and later developmental outcomes measured using standardised assessment tools at term, one and two years’ corrected age. A control group of 150 healthy term-born infants will also be recruited for comparison of outcomes. To examine the effects of parental mental health on developmental outcomes, both parents of preterm and term-born infants will complete standardised questionnaires related to symptoms of anxiety, depression and post-traumatic stress at regular intervals from the first week of their child’s birth until their child’s second birthday. The parent–child relationship will be assessed at one and two years’ corrected age.
Detailing the trajectory of infant neurobehaviour and parental psychological distress following very preterm birth is important not only to identify infants most at risk, further understand the parental experience and highlight potential times for intervention for the infant and/or parent, but also to gain insight into the effect this has on parent–child interaction and child development.
PMCID: PMC4016657  PMID: 24758605
Preterm; Neurobehaviour; Magnetic resonance imaging; Neurodevelopment; Parent mental health; Parent–child interaction
23.  Comparative evaluation of ropivacaine and lignocaine with ropivacaine, lignocaine and clonidine combination during peribulbar anaesthesia for phacoemulsification cataract surgery 
Indian Journal of Anaesthesia  2012;56(1):21-26.
Peribulbar block is the most common type of local anaesthesia administered for cataract surgery, and continuous efforts are on to find a long-acting local anaesthetic (LA) drug with the safest pharmacological profile.
A double-blind, prospective and randomized study was carried out in our institute to compare the anaesthetic effects of ropivacaine with the combination of ropivacaine and clonidine in administration of peribulbar block for phacoemulsification cataract surgery.
A total of 200 patients of both sexes aged 50–80 years of American Society of Anaesthesiologists grade I and II, scheduled for phacoemulsification cataract surgery under monitored anaesthesia care, were enrolled for the study. Patients were assigned into two groups of 100 each; ropivacaine group (R) and ropivacaine clonidine group (RC). Group R received 10 mL of LA solution containing 5 mL of 2% lignocaine, 5 mL of 0.75% ropivacaine and 100 units of hyaluronidase while group RC received 8 mL of a similar mixture with the addition of clonidine 1 μg/kg and saline to make a total volume of 10 mL. Heart rate (HR), mean arterial pressure (MAP), pulse oximetry (SpO2), respiratory rate (RR), intraocular pressure (IOP), eye muscle movement scores and quality of peribulbar block were observed and recorded throughout the study period at regular intervals. At the end of the research project, the data was compiled systematically and was subjected to statistical analysis using the ANOVA test with post hoc significance for continuous variables and Chi-square test for qualitative data. Value of P<0.05 was considered significant and P<0.0001 as highly significant.
Demographic characteristics, SpO2 and RR were comparable in both the groups. Mean HR and MAP were also comparable after a significant variation in the first 2–3 min (P<0.05). Onset and establishment of sensory and motor blocks were significantly earlier in the RC group (P<0.05). IOP decreased significantly during the first 6–7 min in the RC group after the administration of the peribulbar block. Duration of analgesia was prolonged in the RC group (6.5±2.1 h) as compared with the R group (4.2±1.8 h). The side-effect profile revealed a higher incidence of nausea, vomiting, headache and dizziness in Group R, while a considerably higher incidence of dry mouth was observed in Group RC.
Addition of clonidine to ropivacaine not only decreases the total volume of LA to be used but also augments early onset and prolonged offset of sensory analgesia as well as provides smooth operating conditions with a good sedation level as well by providing a wider safety margin of LA.
PMCID: PMC3327065  PMID: 22529415
Cataract; clonidine; peribulbar block; ropivacaine
24.  Comparative evaluation of recovery characteristics of fentanyl and butorphanol when used as supplement to propofol anaesthesia 
Background and Aim:
Narcotics have been used since long as a component of balanced anaesthesia, thus minimizing the anaesthetic requirement both during induction and maintenance as well as attenuating the pressor response during laryngoscopy and intubation. Equally significant is their role in provision of smoother recovery period by minimizing postoperative pain. Other than pain, the factors like postoperative nausea and vomiting (PONV), shivering, sedation and respiratory depression are equally important in recovery from the effects of anaesthetic drugs. The present study aimed at comparing the postoperative recovery characterstics of fentanyl and butorphanol in patients undergoing open cholecystectomy under general anaesthesia.
Materials and Methods:
The present study configured one hundred adults patients of American Society of Anaesthesiologists (ASA) grade 1 or 2 of either sex scheduled to undergo elective open cholecystectomy and were randomly assigned to receive fentanyl (group F; n = 50) or butorphanol (group B; n = 50). Both group were premedicated with midazolam 0.04 mg/kg intravenously followed by injection fentanyl 2 mcg/kg or butorphanol 40 mcg/kg. Standard induction was done with propofol 2 mg/kg and vecuronium 0.1 mg/kg was used for intubation. Anaesthesia was maintained with propofol infusion and 67% nitrous oxide in oxygen. Intraoperative hemodynamic parameters were observed and recorded. Postoperatively analgesia, sedation, PONV, shivering, respiratory depression and recovery score were observed.
The recovery time was less in group F (P > 0.05) while post operative analgesia (P < 0.001) and sedation (P > 0.05) was more in group B. The incidence of respiratory depression was more in group B (P > 0.05). PONV was comparable in both the groups. Postoperative shivering was significantly low in group B (P < 0.05).
It is concluded that besides easy availability and lower cost, butorphanol decreased propofol consumption intraoperatively and provided better analgesia and prophylaxis against shivering in postoperative period.
PMCID: PMC3678702  PMID: 23776820
Butorphanol; fentanyl; propofol; recovery
25.  Anaesthesia and physiological monitoring during in vivo imaging of laboratory rodents: considerations on experimental outcomes and animal welfare 
EJNMMI Research  2012;2:44.
The implementation of imaging technologies has dramatically increased the efficiency of preclinical studies, enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time and testing new therapies. The ability to image live animals is one of the most important advantages of these technologies. However, this also represents an important challenge as, in contrast to human studies, imaging of animals generally requires anaesthesia to restrain the animals and their gross motion. Anaesthetic agents have a profound effect on the physiology of the animal and may thereby confound the image data acquired. It is therefore necessary to select the appropriate anaesthetic regime and to implement suitable systems for monitoring anaesthetised animals during image acquisition. In addition, repeated anaesthesia required for longitudinal studies, the exposure of ionising radiations and the use of contrast agents and/or imaging biomarkers may also have consequences on the physiology of the animal and its response to anaesthesia, which need to be considered while monitoring the animals during imaging studies. We will review the anaesthesia protocols and monitoring systems commonly used during imaging of laboratory rodents. A variety of imaging modalities are used for imaging rodents, including magnetic resonance imaging, computed tomography, positron emission tomography, single photon emission computed tomography, high frequency ultrasound and optical imaging techniques such as bioluminescence and fluorescence imaging. While all these modalities are implemented for non-invasive in vivo imaging, there are certain differences in terms of animal handling and preparation, how the monitoring systems are implemented and, importantly, how the imaging procedures themselves can affect mammalian physiology. The most important and critical adverse effects of anaesthetic agents are depression of respiration, cardiovascular system disruption and thermoregulation. When anaesthetising rodents, one must carefully consider if these adverse effects occur at the therapeutic dose required for anaesthesia, if they are likely to affect the image acquisitions and, importantly, if they compromise the well-being of the animals. We will review how these challenges can be successfully addressed through an appropriate understanding of anaesthetic protocols and the implementation of adequate physiological monitoring systems.
PMCID: PMC3467189  PMID: 22877315
Preclinical imaging; Anaesthesia; Physiological monitoring

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